Role of CYP1A2 polymorphisms in breast cancer risk in women

Abstract

Cytochrome P4501A2 (CYP1A2) is a key enzyme in the etiology of breast cancer (BC). It is involved in breast carcinogen activation [aromatic (AAs) and heterocyclic amines (HAs), polycyclic aromatic hydrocarbons (PAHs)], in the production of beneficial oestrogen [2-hydroxyestrone (2-OHE1)] and in converting arachidonic acid (AAc) to epoxyeicosatrienoic acids (EETs), which have anti-inflammatory properties. Within a hospital-based case-control study, the effect of functional CYP1A2 variants [-3860G/A (rs2069514), -2467T/delT (rs3569413), -163C/A (rs762551)] and their interactions with environmental factors in BC risk was investigated. The study population included 125 BC cases and 43 non-cancer controls. Genotyping was performed in RT-PCR using Taqman assays. The gene-environment interaction was appraised using a case-only study design. We found that the -3860A variant, independently from environmental factors, as well as by interacting with fried foods (p=0.025) and indoor exposure to pollutants (p=0.050), reduced the risk of BC (p=0.025), whereas its interaction with coffee (p=0.045) increased the BC risk. This is the first study indicating that the -3860A variant, by decreasing CYP1A2 activity, modifies BC risk by interacting with environmental factors, thereby supporting the hypothesis that reduced CYP1A2 activity contributes to BC risk in different ways, for example, it may be protective by reducing the activation of pro-carcinogens such as AAs, HAs and PAHs, but would increase risk by reducing the beneficial formation of 2-OHE1 and EETs.

A Comprehensive Overview of the Risks and Benefits of Coffee Consumption

“…Coffee drinking appears to increase the risk of gastric (Galanis and others ) and colorectal cancer in men (Slattery and others ; Boutron‐Ruault and others ; Yamada and others ) but not in women (Lee and others ), although the authors queried if the former was just a chance finding (Galanis and others ). The risk of pancreatic cancer also appears to be higher in smokers (Gorham and others ; Harnack and others ) and nonconsumers of alcohol (Clavel and others ), whilereas genetic polymorphisms (CYP1A2 and GSTM1/GSTT1) can modify the relationship between coffee consumption and risk of breast (Kotsopoulos and others ; Bageman and others ; Ayari and others ), ovarian (Goodman and others ), and skin (Fortes and others , ) cancer. In some instances, only caffeinated coffee appears to be protective when compared with decaffeinated coffee (for example, in skin, endometrial, and some gastric cancers; Abel and others ; Bhoo‐Pathy and others ; Sanikini and others ) but in other studies, the opposite is true (for example, for ovarian, rectal and lung cancers; Michels and others ; Baker and others , ).…”

Genetic Polymorphisms in Estrogen-Related Genes and the Risk of Breast Cancer among Han Chinese Women

“…Another key enzyme of the pathway is CYP1A2, which also plays a crucial role in estrogen metabolism. Genetic variants of CYP1A2 have been shown to contribute to the risk of lung and breast cancer by interacting with environmental factors and drug metabolism through regulation of enzyme activity [37,38,39]. SNP rs2069522 is located at −2847 bp of CYP1A2 , within a putative region that bidirectionally regulates the transcriptional activation of both CYP1A1 and CYP1A2 genes [40].…”

Inhibition of Human Cytochrome P450 Enzymes by Allergen Removed Rhus verniciflua Stoke Standardized Extract and Constituents

“…CYP1A2 is able to metabolize some polycyclic aromatic hydrocarbons (PAHs), a procarcinogen, to carcinogenic intermediates, so that higher CYP1A2 activity may influence the risk of lung cancer and breast cancer [36, 37]. CYP1A2 is also involved in the metabolism of antidepressants drugs and antipsychotic drugs [29].…”